ARNT inhibitor

An ARNT inhibitor is a therapeutic agent designed to target the Aryl hydrocarbon receptor nuclear translocator (ARNT), also known as HIF-1β. ARNT serves as a mandatory dimerization partner for hypoxia-inducible factors HIF-1α and HIF-2α, which are key drivers of oncogenic transcription in clear cell renal cell carcinoma (ccRCC). By disrupting the formation of the HIF-ARNT complex, these inhibitors suppress the expression of hypoxia-responsive genes such as GLUT1, NDRG1, and VEGFa. This approach is particularly significant as a potential strategy to overcome resistance to HIF-2α-selective inhibitors like belzutifan, which can occur through compensatory HIF-1α signaling. Preclinical studies, including research from Cedars-Sinai Medical Center, have demonstrated that ARNT-selective small molecules can effectively inhibit the proliferation of primary human kidney cancer cells across various histological subtypes, including ccRCC and papillary renal cell carcinoma.

Other names

ARNT inhibitorHIF-1β inhibitorAryl hydrocarbon receptor nuclear translocator inhibitor